Obinutuzumab has renal and steroid-sparing benefits in lupus nephritis


By Mardi Chapman

21 Nov 2023

Professor Brad Rovin

The addition of the type II anti-CD20 antibody obinutuzumab to standard-of-care lupus nephritis therapy assists in the long-term preservation of kidney function and prevention of flares, US researchers say.

According to a post hoc analysis of the phase 2 NOBILITY trial, published in Arthritis & Rheumatology [link here] and presented at ACR Convergence 2023, two-years of obinutuzumab treatment significantly reduced the risk of adverse kidney outcomes.

The NOBILITY trial, published last year [link here], found the addition of obinutuzumab to standard therapies of mycophenolate and steroids, improved the rate of complete renal response (CRR) compared to standard therapies alone at 12 months (35% v 23%; p=0.0.115 and at 24 months (41% v 23%; p=0.026).

The investigators also found B-cell depletion with obinutuzumab was not associated with increases in serious adverse events.

Now the post hoc analysis found obinutuzumab significantly reduced the risk of an unfavourable composite kidney outcome (treatment failure, serum creatinine doubling, or death) by 60% (HR 0.40) and a lupus nephritis flare by 57% (HR 0.43).

Obinutuzumab also significantly attenuated eGFR slope declines from baseline – the first 30% eGFR decline by 80% compared to SOC (HR 0.20) and first 40% eGFR decline by 91% (HR 0.09) respectively.

“Given that the main goal of lupus nephritis therapy is to preserve kidney survival, the fact that patients receiving obinutuzumab had eGFR declines of 30 or 40% significantly less often than patients receiving SOC alone suggests that the addition of obinutuzumab to initial lupus nephritis treatment regimens will be of benefit to patients’ long-term kidney health,” the study said.

The investigators also found obinutuzumab had a steroid-sparing effect with more patients in the treated group able to maintain a daily prednisone dose of 7.5 mg or less from week 64 through week 76 and achieve CRR at week 76 (38% v 16%; P < 0.01).

The median cumulative dose of prednisone from weeks 64 through 76 was 525 mg in the obinutuzumab group versus 630 mg in the placebo group.

“…a clinically meaningful reduction in glucocorticoid use is now recognised as an important short-term and long-term treatment goal in patients with lupus nephritis because risks and toxicities associated with glucocorticoid use are numerous,” they said.

“The totality of these data not only confirm the benefit of B cell depletion to short-term treatment outcomes of patients with lupus nephritis, but the results of our analyses have implications for preservation of long-term kidney health.”

Speaking at ACR Convergence 2023, nephrologist and lead author Professor Brad Rovin, from the Ohio State University Wexner Medical Center in Columbus, said the post hoc analysis was important.

“I think that all of us who are involved in clinical trials understand that we go for a one or two year study… and we’re looking for complete renal responses. But what we’re really looking for in my opinion is that we have prolonged kidney survival such that the patients don’t progress on towards the need for renal replacement therapy with transplant or dialysis.”

“So in summary, treatment with obinutuzumab increased complete renal response rates and it decreased the risk of unfavourable kidney outcomes. It reduced the decline in eGFR on a yearly basis, and it reduced the risk of lupus nephritis flare. And this can be done potentially with less glucocorticoid use in these patients.”

He said obinutuzumab had enhanced B cell killing compared to other CD20 antibodies such as rituximab due to glycoengineering with up to 100 times more antibody-dependent cytotoxicity. As well, the type II binding conformation reduced the need for complement-dependent cytotoxicity which was really relevant to patients with lupus nephritis.

He said obinutuzumab was currently being evaluated in the phase 3 REGENCY trial [link here] which has enrolled its last patient.

“So we’ll hopefully see if this supports the phase two data.”

NOBILITY was funded by F. Hoffmann-La Roche Ltd.

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